Increasing numbers of DNA structures are being revealed using a diverse range of transition metal complexes and biophysical spectroscopic techniques. Here we present a review of metal complex-DNA interactions in which several binding modes and DNA structural forms are explored.

The diverse anticancer utility of cisplatin has stimulated significant interest in the development of additional platinum-based therapies, resulting in several analogues receiving clinical approval worldwide. However, due to structural and mechanistic similarities, the effectiveness of platinum-based therapies is countered by severe side-effects, narrow spectrum of activity and the development of resistance. Nonetheless, metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations. This review discusses recent advances in platinum and other transition metal-based complexes with mechanisms of action involving intercalation. This mode of DNA binding is distinct from cisplatin and its derivatives. The metals focused on in this review include Pt, Ru and Cu along with examples of Au, Ni, Zn and Fe complexes; these complexes are capable of DNA intercalation and are highly biologically active.

Linear dichroism spectroscopy probes orientations of interacting molecular systems of known spectroscopy and spectroscopy for those of known geometry.

Eight platinum(II) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I_L)(A_L)]²⁺, where I_L is either dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Me₂dpq) and A_L is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl₂ and [Pt(dpq)(RR-dach)]Cl₂, with IC₅₀ values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO₄)₂·1.75H₂O is also reported.